Clinical Observation of Traditional Chinese Medicine in the Treatment of Diabetic Kidney Disease: A Clinical Case Series

Keywords

Diabetic kidney disease; Shenzhuo formula; Case study; Traditional Chinese medicine.

Abstract

Aim : Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes and the main cause of in end-stage renal disease (ESRD). Conventional clinical treatments for blood glucose, blood pressure, and blood lipid control include ACEI/ARB drugs and other symptomatic treatments, which do not control disease progression. Therefore, in the present study, we assessed the effectiveness of a Chinese medicinal therapy for the treatment of DKD, ameliorating patients’ clinical symptoms, controlling proteinuria, delaying the progression of DKD, and protecting renal function.

Methods : From July 2007 to January 2018, we assessed five DKD patients. We collected data on these patients’ symptoms, physical examination findings, and physicochemical examination findings at multiple visits. Patient medical records were reviewed retrospectively. also improved.

Results : In the five cases reported, clinical symptoms such as edema and urine foam were obviously relieved or even resolved completely. Serum creatinine (Scr) decreased or was maintained, and the 24-hour urinary protein tended to decrease. In the course of treatment, not only were no adverse reactions observed, but patient renal functioning improved or remained stable. Patient quality of life  also improved.

Conclusion : Shenzhuo formula is a promising and safe method for the treatment of DKD and is thus worthy of further controlled clinical and mechanistic studies.

Citation

Zhang L, Ma J, Wei Y, Zhao L, Tong X (2025) Clinical Observa tion of Traditional Chinese Medicine in the Treatment of Diabetic Kidney Disease: A Clinical Case Series. SM J Case Rep 11: 8.

INTRODUCTION

Diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes and is the leading cause of death and the main cause of chronic kidney disease in patients with diabetes, accounting for approximately 30-47% [1], of end-stage renal disease (ESRD). According to the US Renal Data System, ESRD caused by DKD accounts for about 44% of the total number of ESRD in the United States [2]. Among Asian countries, Japan accounts for about 40% [3], South Korea about 48% [4], and China about 19% of ESRD cases. With an aging Chinese population and lifestyle changes, the prevalence of diabetes has reached 10.9%. Chinese diabetes patients now account for 1/3 of all diabetic patients globally, and the incidence of DKD among hospitalized diabetic patients has reached 34.7% in china [5,6]. In 2015, an estimated 415 million people worldwide suffered from diabetes and 5 million died of the disease, and the global Ministry of Health spent a total of US $673 billion [7]. According to data from the International Diabetes Federation in 2017, by 2045, nearly 9.9% of the world’s population or 639 million people will have diabetes, of whom 30–40% will develop DKD [8,9]. DKD seriously affects the quality of life of patients and threatens public health, creating a heavy burden on social, economic, and medical resources. Therefore, it is necessary to identify effective drug treatments that decrease the occurrence and progress of DKD.

According to international DKD guidelines [10], reducing serum creatinine (Scr), increasing endogenous creatinine clearance (Ccr), and controlling proteinuria can delay the progression of DKD. In addition, because DKD patients often have abnormal blood pressure, dyslipidemia, and other diseases, their clinical treatment should not only target Scr, Ccr, albuminuria, and other indicators, but also blood pressure and blood lipid control. Traditional Chinese medicine is a unique medical resource in China, and more and more clinical practices have discovered its unique advantages for improving patients’ signs and symptoms clinical manifestations and physical and chemical indicators. Therefore, it is critical that traditional Chinese medicine is explored further to uncover additional effective and safe treatment methods for the prevention of DKD, protection of renal function, and improved quality of life. The present report describes five patients with DKD and their clinical outcomes after long-term treatment with traditional Chinese medicine. These patients’ symptoms and quality of life improved and their DKD progression was delayed.

METHODS

From July 2007 to January 2018, we assessed five DKD patients who were treated with traditional Chinese medicine for an extended period of time in the Department of Endocrinology at the Chinese Academy of Traditional Chinese Medicine’s Guang’anmen Hospital. We collected data on these patients’ symptoms, physical examination findings, and physicochemical examination findings at multiple visits. Findings were recorded for future analyses (Microsoft Excel, Seattle, WA).

The present study was a retrospective and small sample study based on the real-world clinical recorded data. It was not a prospective study, and the patients’ verbal consent was taken for providing their medical records for analysis and the results of the study. In this study, we have reported only the medical records and statistical results, not including the patients’ privacy information, so we think it did not touch on benefits and harms of patients and ethical approval and written patient consent was not necessary.

CASE PRESENTATION

Case 1

This 63-year-old female patient was 167 cm tall and weighed 82 kg (BMI: 29.40 kg/m2). She first visited the endocrine clinic at our hospital on July 1, 2009. She was diagnosed with DKD, hypertension, and coronary heart disease. She had a 15-year history of type 2 diabetes, hypertension, and coronary heart disease. She was managed medically with Novolin 30R (16 IU in the morning, 8 IU in the evening), levamlodipine benzenesulfonate tablets (2.5 mg, twice daily), aspirin (75 mg, once daily), paracetamol (10 mg, three times daily), Atto vastatin (20 mg, once per night). Her fasting blood glucose fluctuated from 6~8 mmol/L and her blood pressure (BP) from 130~150/65~80 mmHg. She lost more than 5 kg of weight in the first six months of this visit. This patient’s primary clinical manifestations were severe edema of both lower limbs, cold below the knees, blurred vision, numbness in both hands, frequent urination at night (3-4 times per night), and dry stool, once every two days. Her tongue was greasy, the bottom of it stagnant, and her pulse was weak. The patient’s serum creatinine (Scr) was 178 mmol/L, her blood urea nitrogen (BUN) was 16.4 ug/L, her serum uric acid (BUA) was 562 μ/L, and her BP was 150/65 mmHg. Unfortunately, her 24-hour urine was not clear. The patient was administered a traditional Chinese medicine treatment. Her specific prescription included 20 g of Dahuang (Radix Et Rhizoma Rhei Palmati), 30 g of Fuzi (Radix Aconiti Lateralis Preparata; preceded by 2 hours by Decoct), 60 g of Huangqi (Radix Astragali Mongolici), 30 g of Danshen (Radix Salviae Miltiorrhizae), 30 g of Weilingxian (Radix et Rhizoma Clematidis Chinensis), and 120 g of Fuling (Poria).

The patient’s second clinic visit was on July 22, 2009. After 20 days of treatment, the edema in both of her lower limbs was reduced by 50% and her hand and finger numbness was improved. Her labs were as follows: Scr, 179 mmol/L; BUN, 16.94 μ/L; BUA, 491 μ/L; 24HUTP, 1800 mg/24 h; and BP, 140/74 mmHg. Her prescription for traditional Chinese medicine was amended to include 3 g of Shuizhi (Hirudo) and 90 g of Huangqi.

One month later, the patient’s lower limb edema disappeared. Her Scr was 135 mmol/L, BUN was 15.52 μ/L, BUA was 491 um/L, 24HUTP 2210 was mg/L, CHO 7.11 was mmol/L, and blood pressure was 140 mmol/75 mmHg. Her prescription for traditional Chinese medicine was amended to include reduced Poria cocos and added 6 g of Hongqu (Monascus).

As of January 16, 2018, the patient had been treated with traditional Chinese medicine for nearly 9 years. During this period, her prescription was modified according to her main symptoms and physical and chemical indices. Her basic prescription included a Shenzhuo formula (Dahuang, Huangqi, Danshen, Shuizhi, Sanqi). During the follow-up period, her 24 HUTP and Scr were reexamined regularly, as was her estimation of glomerular filtration rate (eGFR), the results of which are shown in Figures 1-3.

Figure 1: After 2 months of treatment with traditional Chinese medicine, the Patient 1’s creatinine decreased gradually and steadily, fluctuating some

Figure 2: Patient 1’s 24-hour urinary protein showed a gradual downward trend.

Figure 3: Patient 1’s glomerular filtration rate increased gradually and then became steady.

Case 2

This 47-year-old male patient was 172 cm tall and weighed 60 kg (BMI: 20.52 kg/m2). He first was seen in the endocrine clinic at our hospital on March 22, 2010. He was diagnosed as DKD, hypertension, and a previous myocardial infarction. The patient’s previous history of type 2 diabetes mellitus was 5 years long, that of hypertension was 2 months long, and that of the prior myocardial infarction was 1 year long. He was treated with acarbose (50 mg, once daily), aspirin (75 mg, once per night), and losartan potassium tablets (50 mg, once daily). His fasting blood glucose fluctuated from 5.5~6.5 mmol/L and his blood pressure from 120~160/80~90 mmHg. At present, this patient’s primary disease manifestations included mild edema in both lower limbs, hunger, low back pain, foam on urination, a fine tongue tremor, stagnation of the bottom of the tongue, a greasy tongue coating, and stiff pulse strings. His Scr was 13 mmol/L, BUN was 10.10 μ/L, BUA was 364 u /L, BP was 150/75 mmHg, and 24HUTP was 260 mg/24 h. The patient was prescribed a traditional Chinese medicine including 9 g of Dahuang, 15 g of Huanglian (Rhizoma coptidis), 15 g of Fuzi (preceded by 2 hours by Decoct), 30 g of Huangqi, 30 g of Danshen, 3 g of Shuizhi, and 15 g of Shengjiang (Zingiber officinale Rose).

After 3 months, the patient’s edema in both lower limbs resolved, his urine foam improved by 50%, and his Scr was 108 mmol/L, BUN was 8.49 μ/L, BUA was 466 μ/L, BP was 126/ 80 mmHg, and 24HUTP was 140 mg/24 h. His prescription was modified to include 30 g of Weilingxian.

From July 5, 2010 to February 4, 2013, the patient was seen 26 times and his condition was deemed stable. His prescriptions were modified from the time of his initial diagnosis. From March to May 2013, the patients was overworked and his urine foam increased. His Scr was 98.8 mmol/L, BUN was 9.89 μ/L, BUA was 411 μ/L, BP was 150/75 mmHg, and 24HUTP was 2580 mg/24 h. The patient’s prescription as again changed to include 60 g of Huangqi, 15 g of Danshen, 6 g of Dahuang, 3 g of Shuizhi, 30 g of Jinyingzi (golden cherry fruit), and 30 g of Qianshi (Euryale fruit).Two months after changing this prescription, the patient’s 24HUTP decreased to 150 mg/24 h.

As of June 28, 2017, the patient had been treated with traditional Chinese medicine for 7 years. During this period, according to his main symptoms, his prescription was composed of a base of Shenzhuo formula. During the follow-up period, the patient’s 24HUTP and Scr were reexamined regularly and his eGFR was assessed, as shown in Figures 4-6.

Figure 4: Patient 2’s creatinine maintained a steady trend.

Figure 5: Patient 2’s 24-hour urinary protein fluctuated, with one prominent peak value that was caused by overwork.

Figure 6: Patient 2’s eGFR as a whole maintained a steady trend.

Case 3

This 76-year-old female patient was 150 cm tall and weighed 50 kg (BMI: 22.22 kg/m2). On July 12, 2007, he was first seen by the endocrine clinic at our hospital and was diagnosed with DKD, hypertension, and chronic pyelonephritis. He had a history of 8 years of type 2 diabetes, 2 years of hypertension, and 35 years of chronic pyelonephritis. This patient did not take any hypoglycemic drugs, but did take amlodipine besylate tablets (5 mg, twice daily), and losartan potassium tablets (50 mg, once daily). His blood pressure fluctuated from 120~150/70~95 mmHg. His primary disease manifestations included excessively hot hands and feet, irritability, numbness and weakness in both lower limbs, a dark red tongue, a yellow and greasy tongue coating, and sinking pulse strings. His Scr was 120 mmol/L, BUN was 8.40 μ/L, BUA was 416 μ/L, BP was 140/80 mmHg, and 24HUTP was 520 mg/24 h. He was given a prescription of traditional Chinese medicine, including 12 g of Huanglian,2 g of Rougui (cinnamon), 30 g of Huangbai (Cortex Phellodendri), 30 g of Zhimu (Anemarrhena), 30 g of Nvzhenzi (Ligustrum lucidum), 30 g of Jinyingzi (golden cherry fruit), 1 g of Dahuang, 6 g of Shuizhi, 30 g of Suanzaoren (wild jujube kernel), and 9 g of Wuweizi (Schisandra chinensis).

From July 2007 to February 2008, the patient was seen 13 times, and his symptoms such as hand and foot heat and irritability gradually improved. His prescription was also modified from the original. On March 10, 2008, the patient’s hand and foot heat resolved, and his primary disease manifestations included irritability, dizziness, unstable blood pressure control, and high blood pressure (160/80 mmHg). His prescription was changed to include 15 g of Tianma (Rhizoma Gastrodiae), 30 g of Gouteng (Ramulus Uncari- ae Rhynchophyllae cum Uncis), 30 g of Chongweizi (Fructus Leonuri Japonici), 30 g of Niuxi (Radix Achyranthis Bidentatae), 3 g of Dahuang, 9 g of Shuizhi, 30 g of Jinyingzi, 30 g of Nvzhenzi, and 30 g of Huangqi. After 2 months, the patient’s blood pressure was controlled and ranged from 120~140/70~85 mmHg.

As of March 2, 2015, the patient had been treated with traditional Chinese medicine for nearly 8 years. During this period, his prescription was composed of Shenzhuo formula given his main symptoms and physical and chemical findings. During the follow-up period, his 24HUTP and Scr were reviewed, as was his eGFR, the results of which are shown in Figures 7-9.

Figure 7: Patient 3’s serum creatinine decreased gradually.

Figure 8: Patient 3’s 24-hour urine protein gradually decreased and fluctuated.

Figure 9: Patient 3’s eGFR exhibited a gradual upward trend.

DISCUSSION

DKD is a chronic kidney disease caused by diabetes. Many factors are involved in DKD’s pathogenesis, including hyperglycemia, which is thought to be the initiating factor. The pathogenesis of DKD is mainly related to adaptive glomerular hyperfiltration, which leads to long term damage to functional nephrons. Its progression is characterized by continuous increases in albuminuria, increases in arterial blood pressure, and decreases in GFR. Prior research reveals that declining rates in GFR vary greatly, and average to about 2~20 mL/ (min·1.73 m2) per year [11]. Although a variety of hypoglycemic, antihypertensive, and other drugs have been developed for DKD, symptomatic treatment remains critical. A new type of hypoglycemic drug, sodium-glucose cotransporter 2 (SGLT2) inhibitors, inhibit the reabsorption of sodium and glucose in the renal tubules, reducing levels of blood glucose and glycosylated hemoglobin and significantly reducing the risk for complex endpoints including major cardiovascular and renal events [12,13]. However, the use of this class of drug should be limited in patients with moderate renal insufficiency, and it is not recommended for use in patients with severe renal insufficiency [14]. In fact, a systematic review by Kohan DE revealed that the SGLT2 inhibitor dapagliflozin was associated with slightly more adverse renal events than a placebo in patients with moderate renal impairments (30 mL/min/1.73 m2 < eGFR <60 mL/min/1.73 m2) or in patients older than 65 years old of age. This suggests that the current therapeutic drugs for patients with moderate and severe renal function injuries in and DKD still have some limitations in delaying the disease progression of the disease and protecting renal function.

In the cases of DKD described in the present study, renal function was moderate or severe and they were treated with traditional Chinese medicine. During the treatment period of 5 to 9 years, their clinical symptoms, including lower limb edema and urine foam, were relieved or even resolved completely. During the follow-up period, Scr either decreased or was maintained, and the 24HUTP, on the whole, tended to decrease. In the course of treatment, not only were no adverse reactions observed, but renal functioning in patients improved or remained stable without a downward trend. Patient quality of life also improved.

DKD belongs to “edema” and “kidney fatigue” in traditional Chinese medicine. We contend that the core pathogenesis of DKD involves qi deficiency, blood stasis, and turbidity. Qi deficiency is the initiating factor, while blood stasis occurs throughout and turbidity is the final outcome. These three mechanisms influence one another and cause disease, damage the kidney collaterals, and lead to DKD.

“Shenzhuo formula” are empirical prescriptions and variants of Didang Tang (a decoction from Shang Han Lun). They are composed of Huangqi, Dahuang, Shuizhi, Danshen, Sanqi, and other ingredients. A previous retrospective analysis by our group of outpatient cases revealed that a Shenzhuo formula could reduce urinary protein and serum creatinine in patients with stage III and IV DKD and significantly increase endogenous creatinine clearance. Further retrospective analyses of stage DKD IV patients revealed showed that the quantity of 24-hour urinary protein decreased significantly after an intervention with traditional Chinese medicine for 1, 1.5, and 2 years, and that there were no abnormal changes in liver function before or after treatment. These results preliminarily demonstrated the clinical efficacy and safety of the Shenzhuo formula.

Huangqi invigorates the qi and increases yang, promotes diuresis and reduces swelling. It adjusts the “qi deficiency” state in DKD. Modern studies [18-21], have also found that astragaloside, the main component of Huangqi, has a variety of functions which can significantly improve renal fibrosis and functional damage by inhibiting TGF- β/Smad, MAPK, Wnt, and TLR4/NF- κ B signal transduction pathways. Zhang et al. conducted a meta-analysis of the use of Huangqi as a monomer or as an extract for the treatment of patients with chronic kidney disease and found that astragalus not only reduced creatinine clearance, but also reduced 24 hour urinary protein levels.

Danshen, Shuizhi, Sanqi, and leeches promote blood circulation, decrease blood stasis, and dredge collaterals, improving static state of DKD. Modern studies [23,24], have also found that Danshen protects the glomerular filtration barrier and reduces renal injury by regulating glucose and lipid metabolism, inflammation, and oxidative stress, and thus delays the occurrence and development of DKD. Furthermore, Shuizhi and Sanqi are commonly used to improve microcirculation. Sanqi also has anti-inflammatory and anti-oxidant effects and protects the vascular endothelium. Shuizhi is a medicine derived from animals that promote anticoagulation and antagonize inflammatory mediators to efficiently remove circulating immune complexes in the body. At the same time, it can significantly reduce the deposition of fibrin-related antigens in glomeruli, delay glomerulosclerosis, reduce proteinuria, and improve renal function [25].

Dahuang decreases blood stasis, removes dampness, relieves turbidity, and improves the “turbid” internal environment in DKD. Dahuang also increases renal perfusion by promoting intestinal peristalsis. Because it not only helps to defecate, but also removes turbidity, Dahuang is especially useful for decreasing DKD-related phlegm, turbid dampness, toxins, and other pathological products. Recent studies [26,27], have also shown that Dahuang inhibits compensatory renal hypertrophy in patients with chronic renal insufficiency and reduces proteinuria. Pharmacological studies [28], have further shown that emodin and Rhein, the main components of Dahuang, reduce diabetic kidney damage by improving blood hypercoagulation and microcirculation. Animal experiments have demonstrated that [29], Rhein may reduce urinary protein and urinary albumin/creatinine ratios and increase endogenous creatinine clearance in T2DM rats.

CONCLUSION

The clinical application of Shenzhuo formula to the treatment of DKD may improve the symptoms and quality of life of patients with DKD by protecting renal function and delaying disease progression without causing drug dependence. Critically, we found that there were no adverse reactions to Shenzhuo formula among the cases assessed here. This case report aims to evidence a novel approach for the treatment of DKD. Whether long-term treatment with traditional Chinese medicine can protect renal function, delay DKD progress, and the safety of long-term application of traditional Chinese medicine requires additional study and evaluation.

DECLARATIONS

Ethics approval and consent to participate

The present study was a retrospective and small sample study based on the real-world clinical recorded data. It was not a prospective study, and the patients’ verbal consent was taken for providing their medical records for analysis and the results of the study. In this study, we have reported only the medical records and statistical results, not including the patients’ privacy information, so we think it did not touch on benefits and harms of patients and ethical approval and written patient consent was not necessary.

AVAILABILITY OF DATA AND MATERIALS

The data that support the findings of this study are stored in Guang’anmen Hospital (Beijing, China) and available from the corresponding authors on reasonable request.

FUNDING

Supported by Beijing Natural Science Foundation (7244497); the Clinical Research Center Construction Project of Guang’anmen Hospital, CACMS (Grant No. 2022LYJSZX01); the Clinical Research Center Construction Project of Guang’anmen Hospital, CACMS (Grant No.2022LYJSZX28); the Central Public Welfare Research Institutes (No. ZZ16-XRZ-042); Young Elite Scientists Sponsorship Program by CACM CACM-2023-QNRC2-A08)The Escort Project of Guang’anmen Hospital, China Academy of Chinese Medical Sciences (Backbone Talent Training Project) (Grant No. GAMHH9324025).

AUTHORS’ CONTRIBUTIONS

Lili Zhang, Jiang Ma and Yu Wei interpreted the data and drafted the manuscript. Xiaolin Tong and Linhua Zhao revised the manuscript. Yu Wei, and Rumeng Tang participated in the data collection. All authors read and approved the manuscript.

ACKNOWLEDGEMENTS

We thank these patients and their family for publication of this case report.

REFERENCES

1. Sharma D, Bhattacharya P, Kalia K, Tiwari V. Diabetic nephropathy: New insights into established therapeutic paradigms and novel molecular targets. Diabetes Res Clin Practice. 2017; 128: 91-108.

2. USRDS. ESRD in the United States: An Overview of USRDS Annual Data. Report. USA: United States Renal Data System; 2014.

3. Yamagata K, Iseki K, Nitta K, Imai H, Iino Y, Matsuo S, et al. Chronic kidney disease perspectives in Japan and the importance of urinalysis screening. Clin Exp Nephrol. 2008; 12: 1-8.

4. Jin Dc, Yun Sr, Lee Sw, Han Sw, Kim W, Park J, et al. Lessons from 30 years’ data of Korean end-stage renal disease registry, 1985-2015. Kidney Res Clin Practice. 2015; 34: 132-139.

5. Zuo L, Wang M. Current burden and probable increasing incidence of ESRD in China. Clin Nephrol. 2010; 74: S20-22.

6. Wang L, Gao P, Zhang M, Huang Z, Zhang D, Deng Q, et al. Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013. JAMA. 2017; 317: 2515-2523.

7. Ogurtsova K, Da Rocha Fernandes Jd, Huang Y, Linnenkamp U, Guariguata L, Cho Nh, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Practice. 2017; 128: 40-50.

8. Cho Nh, Shaw Je, Karuranga S, Huang Y, Da Rocha Fernandes Jd, Ohlrogge Aw, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Practice. 2018; 138: 271-281.

9. Gnudi L, Coward Rjm, Long Da. Diabetic Nephropathy: Perspective on Novel Molecular Mechanisms. Trends in endocrinology and metabolism: TEM. 2016; 27: 820-830.

10. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis. 2007; 49: S12-154.

11. Guo KF, Chen HB, JWP. Advances in Epidemiology of Diabetic Kidney Disease. J Med Res. 2015; 44: 162-166.

12. Zinman B, Wanner C, Lachin Jm, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. The New Engl J Med. 2015; 373: 2117-2128.

13. Neal B, Perkovic V, Matthews Dr. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. The New Engl J Med. 2017; 377: 2099.

14. Diabetes Branch of Chinese Medical Association. Guidelines for the Prevention and treatment of Type 2 Diabetes in China (2017 Edition). Chin J Diabetes Mellitus. 2018; 10: 4-67.

15. Kohan De, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016; 29: 391-400.

16. Tian J, Zhao L, Zhou Q, Liu W, Chen X, Lian F, et al. Efficacy of Shenzhuo formula on diabetic kidney disease: a retrospective study. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan. 2015; 35: 528-36.

17. Chen H, Guo J, Zhao X, He X, He Z, Zhao L, et al. Retrospective analysis of the overt proteinuria diabetic kidney disease in the treatment of modified Shenzhuo formula for 2 years. Med. 2017; 96: e6349.

18. Che X, Wang Q, Xie Y, Xu W, Shao X, Mou S, et al. Astragaloside IVsuppresses transforming growth factor-β1 induced fibrosis of cultured mouse renal fibroblasts via inhibition of the MAPK and NF-κB signaling pathways. Biochem Biophys Res Communication. 2015; 464: 1260-1266.

19. Wang L, Chi Yf, Yuan Zt, Zhou Wc, Yin Ph, Zhang Xm, et al. Astragaloside IV inhibits the up-regulation of Wnt/β-catenin signaling in rats with unilateral ureteral obstruction. Cellular Physiol Biochem. 2014; 33: 1316-1328.

20. Wang L, Chi Yf, Yuan Zt, Zhou Wc, Yin Ph, Zhang Xm, et al. Astragaloside IV inhibits renal tubulointerstitial fibrosis by blocking TGF-β/Smad signaling pathway in vivo and in vitro. Exp Biol Med (Maywood, N.J.). 2014; 239: 1310-1324.

21. Zhou X, Sun X, Gong X, Yang Y, Chen C, Shan G, et al. Astragaloside IV from Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кB in vivo and in vitro. Int Immunopharmacol. 2017; 42: 18-24.

22. Zhang Hw, Lin Zx, Xu C, Leung C, Chan Ls. Astragalus (a traditional Chinese medicine) for treating chronic kidney disease. The Cochrane database of systematic reviews. 2014; 2014: CD008369.

23. Zhou X, Razmovski-Naumovski V, Chang D, Li C, Kam A, Low M, et al. Synergistic Effects of Danshen (Salvia Miltiorrhiza Radix et Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma) Combination in Inhibiting Inflammation Mediators in RAW264.7 Cells. BioMed Res Int. 2016; 2016: 1-12.

24. Zhou X, Razmovski-Naumovski V, Chan K. A multivariate analysis on the comparison of raw notoginseng (Sanqi) and its granule products by thin-layer chromatography and ultra-performance liquid chromatography. Chinese Med. 2015; 10: 1-13.

25. Yang HY, Du ZH, Bai XJ. Research progress on pharmacological effects of leeches. J Northeast Agricultural University. 2012, 43: 128-133.

26. Yang SL, Zhao XC. Effect of rhubarb on urinary protein excretion rate in elderly. patients with type 2 diabetes mellitus. J Changzhi Med College. 2000; 14: 177-179.

27. Sun HQ, Li JP, Liu LH, Yang CF, Zuo WM, Li CH. Research Progress on Chemical constituents and Pharmacological Action of Rhubarb. Qinghai Grass Industry. 2018; 27: 47-51.

28. Wu Yu X. Study on the Application of Rhubarb in the treatment of Diabetic. Nephropathy. Clin Res Traditional Chinese Med. 2013; 5: 29-30.

29. Hu J, Miao J, Duan Shu F, Wang YL, Li NJ, Zou YT. Protective effect of Rhein on type 2 diabetic rats. China Pharm. 2014; 25: 2113-2116.